Effects of an ergosterol synthesis inhibitor on gene transcription of terpenoid biosynthesis in Blakeslea trispora.

Highly efficient induction of carotene biosynthesis of Blakeslea trispora by ketoconazole (KCZ), an inhibitor of ergosterol biosynthesis, was found previously. To get some insight into the regulatory mechanisms of KCZ controlling terpenoid (including carotene) biosynthesis, the transcript levels of gene hmgR, encoding HMGR, which initiates the biosynthesis of all terpenoids, and gene carRA, encoding lycopene cyclase and phytoene synthase in the carotene biosynthsis pathway, were investigated in B. trispora cells treated with KCZ. Upon KCZ treatment, up-regulation of hmgR and carRA genes, increased beta-carotene and ubiquinone contents, and decreased ergosterol content were all observed. The results suggest that the inhibition of ergosterol biosynthesis by KCZ triggered hmgR gene transcription, which might present a positive feedback regulation of gene hmgR in response to a depletion of ergosterol. Furthermore, KCZ could be used as a new agent to improve not only beta-carotene but also ubiquinone production, whose regulatory mechanisms controlling terpenoid biosynthesis differ from the agents reported previously.